Insulin-Induced Decreases in Aortic Wave Reflection and Central Systolic Pressure Are Impaired in Type 2 Diabetes

Abstract

OBJECTIVE -To determine whether large arteries are resistant to insulin.RESEARCH DESIGN AND METHODS -Insulin normally acutely decreases central systolic pressure by decreasing wave reflection in vivo. This effect occurs before any changes in peripheral vascular resistance or heart rate under normoglycemic conditions. We determined whether the ability of insulin to decrease central aortic pressure is altered in uncomplicated type 2 diabetes. The study subjects consisted of 16 type 2 diabetic patients (age 54 Ϯ 2 years, BMI 29 Ϯ 1 kg/m 2 ) and 19 matched nondiabetic individuals (51 Ϯ 2 years, 29 Ϯ 1 kg/m 2 ) studied under normoglycemic-hyperinsulinemic conditions. Central aortic pressure waveforms were synthesized from those recorded in the periphery using applanation tonometry and a validated reverse transfer function to construct the central aortic pressure waveform every 30 min. This method allowed determination of aortic augmentation (the pressure difference between the first and second central systolic pressure waves) and the augmentation index (augmentation divided by pulse pressure).RESULTS -Whole-body insulin sensitivity was 31% lower (P Ͻ 0.05) in the type 2 diabetic patients than in the normal subjects. Basally, before the insulin infusion, augmentation averaged 8.9 Ϯ 1.3 and 11.1 Ϯ 1.2 mmHg (NS) and the augmentation index averaged 23.1 Ϯ 2.1 and 27.5 Ϯ 2.1% (NS) in the normal subjects and diabetic patients, respectively. After 30 min of hyperinsulinemia, augmentation decreased significantly to 6.1 Ϯ 1.1 mmHg (P Ͻ 0.001) in the normal subjects but remained unchanged at 9.1 Ϯ 1.1 mmHg (NS) in type 2 diabetic patients. At 30 min, the augmentation index had decreased significantly (30 Ϯ 7% decrease) to 17.9 Ϯ 2.6% in the normal subjects but remained at 24.4 Ϯ 2.4% in the diabetic patients (13 Ϯ 4% decrease, P Ͻ 0.05 for change vs. normal subjects). Central systolic pressure decreased significantly by 30 min in the normal subjects but only after 120 min in the type 2 diabetic patients. There were no significant changes in heart rate, pulse pressure, or forearm blood flow during the first 120 min of the insulin infusion.CONCLUSIONS -Insulin resistance in type 2 diabetes involves a delay in the ability of insulin to decrease central aortic pressure. This defect could predispose these patients to develop systolic hypertension.

Influence of meal intake on pulse wave indices in type 2 diabetes

“…This finding is also consistent with an earlier study showing decrease in AI under the insulin clamp technique, whereas no significant relation between D AI and changes in glucose or insulin levels. 29 These results support the hypothesis that postprandial hemodynamic changes may affect baPWV and AI more directly than the other changes including biochemical, hormonal and autonomic changes.…”

Ambulatory Blood Pressure Monitoring in Lean, Obese and Diabetic Children and Adolescents

“…Acute administration of insulin has been shown to have vasodilatory effects. In normal men, infusion of physiologic doses of insulin decreases the augmentation index within 1 h, consistent with increased distensibility or vasodilatation of large arteries, whereas the vasodilatory response to insulin in patients with T2DM occurred after 2 h, suggesting that the delayed insulin action due to IR could predispose patients with diabetes to develop systolic hypertension [24]. …”

Association of Serum–Free Fatty Acid Level With Reduced Reflection Pressure Wave Magnitude and Central Blood Pressure

“…Insulin resistance and diabetic status have been shown to be favorably associated with AIx and central BP in observational studies in patients with diabetes mellitus 22,23 and general populations, 9,13 as well as in an experimental study using a euglycemic insulin clamp technique. 24 We also reported that not only increased insulin resistance but also reduced insulin sensitivity assessed by an oral glucose tolerance test were factors that Values are mean±standard deviation.…”